Synthesis of Prostate-Specific Membrane Antigen-Targeted Bimodal Conjugates of Cytotoxic Agents and Antiandrogens and Their Comparative Assessment with Monoconjugates

• Published in: International journal of molecular sciences Vol. 24; no. 14; p. 11327
• Main Authors: Zyk, Nikolai Y., Garanina, Anastasiia S., Plotnikova, Ekaterina A., Ber, Anton P., Nimenko, Ekaterina A., Dashkova, Natalia S., Uspenskaia, Anastasiia A., Shafikov, Radik R., Skvortsov, Dmitry A., Petrov, Stanislav A., Pankratov, Andrey A., Zyk, Nikolai V., Majouga, Alexander G., Beloglazkina, Elena K., Machulkin, Aleksei E.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.07.2023; MDPI
• Subjects: Amino acids; Antiandrogens; Antigens; Cancer therapies; Comparative analysis; Drugs; Health aspects; Ligands; Peptides; Prostate; Prostate cancer; Proteins; Russia; bimodal conjugates; targeted drug delivery; prostate cancer; monomethyl auristatin E; prostate-specific membrane antigen
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241411327

Prostate cancer is the second most common cancer among men. We designed and synthesized new ligands targeting prostate-specific membrane antigen and suitable for bimodal conjugates with diagnostic and therapeutic agents. In vitro studies of the affinity of the synthesized compounds to the protein target have been carried out. Based on these ligands, a series of bimodal conjugates with a combination of different mitosis inhibitors and antiandrogenic drugs were synthesized. The cytotoxicity of the compounds obtained in vitro was investigated on three different cell lines. The efficacy of the two obtained conjugates was evaluated in vivo in xenograft models of prostate cancer. These compounds have been shown to be highly effective in inhibiting the growth of PSMA-expressing tumors.